In this study, we report the results of an all-atom molecular dynamics
(MD) based simulation that elucidates the effect of pore size and
interactions on the aggregation of paracetamol in polyethylene glycol
diacrylate (PEGDA) polymers. Recent experimental studies (J. Am. Chem.
Soc. 2011, 133, 3756-3759) have shown that nucleation rate of
paracetamol is highest in one of the PEGDA polymers (PEG200DA) but lack
clear understanding of the factors responsible for this anomaly. Our
simulation results show that paracetamol aggregation is predominantly
governed by the size of PEGDA pores and that the polymer paracetamol
interactions play a secondary role. The probability of formation of
paracetamol aggregates, especially of size four, is highest for pore
sizes in the range of 14-25 angstrom, and the drug-drug angle
distributions in all the PEGDA polymers that we have studied here have
characteristics of both forms I and II of paracetamol crystals. We also
demonstrate that the pores in PEGDA polymers can be further engineered
by the use of a suitable solvent concentration to achieve pore sizes
optimal for improved paracetamol aggregation.